Neurophysiological experiments are proposed which will utilize the in vitro hippocampal slice preparation to investigate basic, intracellular correlates of aging in the mammalian (rat) brain. Additionally, all animals studied neurophysiologically will first be assessed on a battery of behavioral tests known to be affected either by aging or by hippocampal lesions. The proposed studies are a direct extension of ongoing work on mammalian brain aging. In this project, we previously characterized a consistent and specific extracellular neurophysiological correlate of hippocampal aging; i.e., the failure of the CA1 monosynaptic population spike to follow prolonged orthodromic, repetitive stimulation. Age-dependent differences, however, were not seen during repetitive, antidromic, or single-pulse stimulation. Some aspects of the neurophysiological age changes were also found to be significantly correlated with the degree of age-related impairment on an active avoidance task (r equals plus .75, p less than .01). The basic goals of this project, then, will be to characterize a behaviorally-correlated fundamental and early neurophysiological change in the hippocampus during aging. Stimulation paradigms similar to those which were effective in the prior study of the extracellular correlate will be employed to investigate more basic intracellular and ionic phenomena, the study of which is greatly facilitated in the hippocampal slice. Concomitantly, our earlier results on neurophysiological-behavioral correlations will be extended by substantially expanding the n, and by employing more sensitive behavioral tests. If time permits, a number of pharmacological agents suggested by the literature will be employed in attempts to manipulate these neurophysio-behavioral phenomena, in vivo.